WO2020076103A1 - Composition for inhibiting cortisone reductase - Google Patents

Abstract

Provided is a composition for inhibiting cortisone reductase, comprising a compound represented by a specific chemical formula as an active ingredient.

Description

Composition for inhibiting cortisone reductase

The present disclosure relates to a composition for inhibiting cortisone reductase.

Stress has been referred to as a source of panacea since ancient times, and especially in modern society, it occurs excessively, regardless of age or gender, due to various causes such as social factors such as academic, work, marriage, and childcare, and environmental factors such as weather and traffic. It is recognized as a very important social problem.

With the rapid development and diversification of our society, as the roles required of modern people increase, people who complain of general anxiety disorders and mental disorders caused by various stresses are increasing. According to the 2006 Epidemiological Survey of Mental Illness, published by the Ministry of Health and Welfare, the percentage of people with more than one mental illness experienced in one year in 2006 was 17.1%. This is about 1 in 6 adults over the age of 18 and under 64, and the lifetime prevalence rate of one or more mental illnesses as of 2006 was 30%, one in three adults. Considering the recent trend of adolescent mental illness due to excessive school fever or various stresses, the prevalence of the entire population can be said to be higher.

Currently, clinical treatment treats anxiety by combining drug therapy and long-term psychotherapy. In the case of drug therapy, such as diazepam, lorazepam, clonazepam, and alprazolam are mainly used. Anti-anxiety drugs of the benzodiazepine type are mainly used, and azapirone-based buspirone is used as a drug to selectively relieve anxiety symptoms by acting on the serotonin receptor selectively. Is becoming In addition, recently, studies on stress regulators derived from natural products capable of supplementing the side effects of these drugs have been actively conducted.

The present inventors continued research on substances derived from asthma that can prevent or treat mental stress-related diseases, and after treatment of mental stress, 11β-hydroxysteroid dehydrogenase, a cortisone reductase of keratinocytes present in the epidermis It was confirmed that type 1 is activated to increase the concentration of cortisol in the epidermis (increasing the degree of reduction of cortisone to cortisol), and the phenomenon of deterioration of skin barrier function caused by activation of the 11β-hydroxysteroid dehydrogenase type 1 is caused by mental stress. It was also confirmed that the mechanism of action is completely different from the phenomenon caused by other causes (eg, physical injury or aging) that are not caused. Furthermore, it was confirmed that a specific compound extracted from soybean specifically inhibited the activity of the 11β-hydroxysteroid dehydrogenase type 1, thereby completing the present invention.

On the other hand, the prior art of a skin protective composition having the same lipid composition and structural properties as a biomembrane existing in human intercellular cells has been disclosed in Korean Patent Publication No. 2001-0011241, which is ceramide, cholesterol and fatty acid. In addition to focusing only on the method of manufacturing a composition based on, as well as containing simple ceramides that are difficult to apply to cosmetics due to solubility problems, there is no liquid crystal form of emulsifying particles, so the stability and moisturizing power of the formulation is reduced. This is caused, there is a problem that the stability of the formulation after manufacture is lowered. In addition, since the composition was prepared by simply mixing substances similar to the composition of the skin lipid, there was a limitation in the ability to penetrate the skin and to moisturize the skin.

Furthermore, by inhibiting the activation of cortisone reductase (11β-hydroxysteroid dehydrogenase 1) due to mental stress, which is not attributable to physical injury or aging, including the above-described conventional invention to date, a substance capable of preventing or treating a decrease in skin barrier function Nothing is known about.

In one embodiment, by inhibiting the activity of 11β-hydroxysteroid dehydrogenase type 1, which is a factor that decreases skin barrier function caused by mental stress, the concentration of cortisol caused by mental stress is reduced, thereby reducing the recovery time of the barrier function of the stratum corneum. It is to provide a (cosmetic) composition that can be made.

According to one embodiment, to provide a composition for inhibiting cortisone reductase containing the compound represented by the following formula (1) as an active ingredient.

[Formula 1]

In Chemical Formula 1,

R ¹ to R ⁸ are each independently a hydrogen atom or a hydroxy group, and at least one of R ¹ to R ⁸ is necessarily a hydroxy group.

In Chemical Formula 1, R ¹ and R ³ are each independently a hydrogen atom, and R ² and R ⁴ to R ⁸ may be each independently a hydroxy group.

The compound represented by Chemical Formula 1 may be a soybean extract.

The cortisone reductase may be 11β-hydroxysteroid dehydrogenase type 1.

The compound represented by Chemical Formula 1 may be included in a concentration range of 0.01 μg / ml to 1,000 μg / ml.

The composition may be a cosmetic composition.

According to one embodiment, by inhibiting the activity of 11β-hydroxysteroid dehydrogenase type 1, which is a factor causing a decrease in skin barrier function due to mental stress, the concentration of cortisol caused by mental stress is reduced, and the barrier function recovery time of the stratum corneum Can be shortened. That is, it is possible to specifically prevent and treat the phenomenon of skin barrier function deterioration caused by mental stress among various causes of skin barrier function deterioration.

1 is a result of measuring the concentration of cortisol in a cell culture medium using an ELISA method.

Figure 2 is a result of RT-qPCR to confirm the gene expression of keratinocyte differentiation marker keratin 10.

3 is a result of RT-qPCR for confirming gene expression of keratin 1, a keratinocyte differentiation marker.

Hereinafter, embodiments of the present invention will be described in detail so that those skilled in the art to which the present invention pertains can easily practice. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein.

Improvement of skin barrier function in the present specification means to decrease the concentration of cortisol by inhibiting the activity of 11β-hydroxysteroid dehydrogenase type 1 present in the damaged skin area due to mental stress, due to physical trauma or aging. It has nothing to do with suppressing oxidative stress or maintaining skin homeostasis. This is because suppressing oxidative stress due to physical trauma or aging or maintaining skin homeostasis is not due to mental stress, and the mechanism is completely different.

In addition, mental stress in the present specification is different from neurosis referred to in the pharmaceutical field, and the neurosis means a misaligned state because it cannot properly adapt to psychosis, but mental stress in the specification is psychosisless Adapted to, but regardless of the will of the party, cortisone reductase (11β-hydroxysteroid dehydrogenase type 1) of keratinocytes in the epidermis means the activated state.

When a portion of a layer, film, region, plate, or the like is used herein as being "above" another portion, this includes not only the case where another portion is "directly above" but also another portion in the middle. Conversely, when one part is "just above" another part, it means that there is no other part in the middle.

In the present specification, unless otherwise defined, "combination" means a mixture or copolymerization. Also, "copolymerization" means block copolymerization or random copolymerization, and "copolymer" means block copolymerization or random copolymerization.

Hereinafter, a composition for inhibiting cortisone reductase according to one embodiment is described.

The composition for inhibiting cortisone reductase according to one embodiment includes a compound represented by the following Chemical Formula 1 as an active ingredient.

[Formula 1]

In Chemical Formula 1,

R ¹ to R ⁸ are each independently a hydrogen atom or a hydroxy group, and at least one of R ¹ to R ⁸ is necessarily a hydroxy group.

For example, in Chemical Formula 1, R ¹ and R ³ are each independently a hydrogen atom, and R ² and R ⁴ to R ⁸ may be each independently a hydroxy group.

Since the compound represented by Chemical Formula 1 has an effect of specifically inhibiting the activity of cortisone reductase present in keratinocytes in the epidermis under mental stress conditions, the composition according to one embodiment functions as a skin barrier even under mental stress conditions. It is possible to prevent the deterioration or to improve the skin barrier function weakened due to mental stress quickly.

Specifically, when mental stress is experienced, wound healing is delayed and skin barrier function is reduced, so that the stratum corneum is reduced in rigidity or recovery of the barrier function after injury is delayed. One is that glucocorticoids (GC), which have increased secretion into the blood through activation of the hypothalamus pituitary adrenal axis (HPA axis) due to mental stress, are present in the peripheral tissues of the epidermis and dermis. By binding to the GC receptors (GR), skin barrier function decreases. In the other, mental stress activates cortisone reductase (11β-hydroxysteroid dehydrogenase 1) of keratinocytes present in the epidermis, thereby increasing the concentration of cortisol (activated GC form), resulting in decreased skin barrier function. The composition according to one embodiment may prevent the deterioration of skin barrier function by inhibiting the activation of cortisone reductase (11β-hydroxysteroid dehydrogenase 1) in the second mechanism.

For example, the compound represented by Chemical Formula 1 may be a soybean extract. The compound represented by the formula (1) may be a rice extract, the compound represented by the formula (1) derived from rice can also be used as a cosmetic composition, but it only serves to improve the moisturizing properties, and is not only used for mental stress. Related, it does not play a role in inhibiting the activation of cortisone reductase (11β-hydroxysteroid dehydrogenase 1). That is, when the compound represented by Chemical Formula 1 is an extract derived from soybean, the activation of cortisone reductase (11β-hydroxysteroid dehydrogenase 1) can be most effectively inhibited. And, when the compound represented by the formula (1) is extracted from a material other than soybean, compared with the case where the compound represented by the formula (1) is extracted from soybean, the mechanism of action to strengthen the skin barrier is completely different. Do.

The cortisone reductase may be 11β-hydroxysteroid dehydrogenase type 1. The compound represented by Formula 1 extracted from soybeans included as an active ingredient in the composition according to one embodiment is characterized by acting on 11β-hydroxysteroid dehydrogenase type 1, thereby inhibiting the activity of the cortisone reductase .

Accordingly, one embodiment provides a composition for inhibiting cortisone reductase, specifically, 11β-hydroxysteroid dehydrogenase type 1 activity, comprising the compound represented by Formula 1 extracted from the soybean as an active ingredient, It may contain a pharmaceutically effective amount of the compound represented by Formula 1 alone or may include one or more pharmaceutically acceptable carriers, excipients or diluents.

The beans may include beans selected from soybean peas and green beans, germinated beans germinating from the beans, or a combination thereof. Specifically, as a composition for inhibiting cortisone reductase according to one embodiment, a compound represented by Formula 1 or a natural product containing the compound represented by Formula 1 and an extract thereof may be used as an active ingredient, and the Formula 1 The compound represented by or a natural product containing the compound represented by the formula (1) and extracts thereof can be obtained from soybeans selected from soybean peas and mung beans, germinated beans sprouted from the beans, or a combination thereof. In addition, the extract of the natural product containing the compound represented by the formula (1) is concentrated by extracting the natural product containing the compound represented by the formula (1) by cold or warming at room temperature with 70% ethanol, and then concentrated again in water. Disperse and fractionate with one or two or more solvents selected from the same amount of hexane, dichloromethane, chlorform, ethyl acetate, butanol, ethanol, methanol, and water to obtain an extract of the natural product containing the compound represented by Formula 1 You can. However, the extraction method is not limited thereto, and any extraction method in which the compound represented by Chemical Formula 1 is contained in the final extract may be used.

The compound represented by Formula 1 in the composition may be included in a concentration range of 0.01 ㎍ / ml to 1,000 ㎍ / ml. When the compound represented by Formula 1 is used at a concentration of less than 0.01 µg / ml, the effect of proliferation and migration of epidermal keratinocytes is insignificant and thus cannot have an effect of improving skin barrier function, and the compound represented by Formula 1 When is used at a concentration of more than 1,000 μg / ml, it is not preferable because cytotoxicity may appear and may harm the human body.

In the above, "a pharmacologically effective amount" refers to an amount sufficient for the physiologically active ingredient to be administered to an animal or human to exhibit a desired physiological or pharmacological activity. However, the pharmaceutically effective amount may be appropriately changed according to the severity of symptoms, the age of the patient, weight, health status, sex, administration route, and treatment period.

In addition, "pharmaceutically acceptable" in the above refers to physiologically acceptable and does not cause an allergic reaction such as gastrointestinal disorder, dizziness or similar reaction when administered to humans. Examples of the carrier, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, Polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In addition, fillers, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers and preservatives may be further included.

For example, the composition may be a cosmetic composition.

In the present specification, "cosmetics" may mean not only cosmetic functions, but also all substances that may have additional medical functions in addition to cosmetic functions.

The formulation of the cosmetic composition is not particularly limited, and may be appropriately selected according to the purpose.

For example, the cosmetic composition is formulated as a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleaning, oil, powder foundation, emulsion foundation, wax foundation and spray, etc. It may be, but is not limited to this. More specifically, cosmetic compositions such as detergents, tonics, hairdressers, nutrients, essences, serums, treatments, conditioners, shampoos, lotions, wool or hair dyes, oil-in-water (O / W), water-in-oil (O / W) can be formulated as a basic cosmetic. In addition, the composition, other ingredients in addition to the above-described essential ingredients in each formulation can be appropriately selected and blended without difficulty by those skilled in the art according to the type or purpose of use of other external agents. For example, it may further include a sunscreen, a hair conditioning agent, fragrance, and the like.

The cosmetic composition may contain a cosmetically acceptable medium or base. These are all formulations suitable for topical application, for example solutions, gels, solid or dough anhydrous products, emulsions, suspensions, microemulsions, microcapsules, microgranules or ionic (liposomes) obtained by dispersing an oil phase in an aqueous phase and / or It may be provided in the form of a non-ionic vesicle dispersant, or in the form of a cream, skin, lotion, powder, ointment, spray or conceal stick. These compositions can be prepared according to conventional methods in the art.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizer or emulsifier is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan.

When the formulation of the present invention is a suspension, liquid diluents such as water, ethanol or propylene glycol as carrier components, ethoxylated isostearyl alcohol, suspensions such as polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystals Sex cellulose, aluminum metahydroxide, bentonite, agar or trakant, etc. can be used.

When the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, trakant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide, etc. may be used as a carrier component. You can.

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder can be used as a carrier component, and in the case of a spray, additionally chlorofluorohydrocarbon, propane / Propellant such as butane or dimethyl ether.

In one embodiment of the present invention, the cosmetic composition may additionally contain a thickener. The thickener included in the cosmetic composition of the present invention is methyl cellulose, carboxy methyl cellulose, carboxy methyl hydroxy guanine, hydroxy methyl cellulose, hydroxyethyl cellulose, carboxy vinyl polymer, polyquaternium, cetearyl alcohol, stearic acid, Carrageenan or the like can be used, preferably, one or more of carboxy methyl cellulose, carboxy vinyl polymer, and polyquaternium can be used, and most preferably carboxy vinyl polymer.

In one embodiment of the present invention, the cosmetic composition may contain various bases and additives as necessary, and the types and amounts of these components can be easily selected by the inventor. If necessary, it may contain an acceptable additive, for example, it may further include components such as preservatives, pigments, additives, etc., which are customary in the art.

Preservatives may be specifically phenoxyethanol (Phenoxyethanol) or 1,2-hexanediol (1,2-Hexanediol), and the like, the fragrance may be artificial flavoring.

And, in one embodiment of the present invention, the cosmetic composition may include a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingo lipids, and seaweed extract. Other ingredients that may be added include fats and oils, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, fungicides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, flavors, And blood circulation accelerators, cooling agents, limiting agents, and purified water.

In addition, the compounding component which may be added in addition is not limited to this, and any of the above components can be compounded within a range not impairing the object and effect of the present invention.

Furthermore, the cosmetic composition according to one embodiment may be used as a pharmaceutical composition as described above, as well as a health functional food. For example, it can be easily utilized as a main raw material, an auxiliary raw material, a food additive, a functional food or beverage.

The "food" refers to a natural product or a processed product that contains one or more nutrients, and preferably means a state that can be directly eaten after a certain processing process, and in a general sense, food It includes food additives, functional foods and beverages.

Foods to which the food composition can be added include, for example, various foods, beverages, gums, teas, vitamin complexes, and functional foods. In addition, special nutritional foods (e.g., dairy products, English, baby food, etc.), processed meat products, fish meat products, tofu, jelly, noodles (e.g. ramen, noodles, etc.), breads, health supplements, seasoned foods (e.g. soy sauce) , Miso, red pepper paste, mixed sauce, etc.), sauces, confectionery (e.g. snacks), candy, chocolate, gum, ice cream, dairy products (e.g. fermented milk, cheese, etc.), other processed foods, kimchi, pickled foods (various kimchis) , Pickles, etc.), beverages (eg, fruit drinks, vegetable drinks, soy milk, fermented drinks, etc.), natural seasonings (eg, ramen soup, etc.). The food, beverage or food additive may be prepared by a conventional manufacturing method.

In addition, the "functional food" or "health functional food" means a food group or a living body having a food composition that gives added value to act and express the function of the food for a specific purpose by using physical, biochemical, or biotechnological techniques. Refers to foods designed and processed to sufficiently express the body's regulation functions for defense rhythm control, disease prevention and recovery, etc. Specifically, it may be a health functional food. The functional food may include a food-acceptable food supplement additive, and may further include suitable carriers, excipients, and diluents commonly used in the production of functional foods.

The type of the dietary supplement is not limited thereto, but may be in the form of powder, granule, tablet, capsule or beverage.

Advantages and features of the present invention, and a method of achieving them will be apparent with reference to embodiments described below in detail. Hereinafter, the present invention will be described in detail by examples. However, these examples are intended to illustrate the present invention in detail, and the scope of the present invention is not limited to these examples.

(Example)

Test Example 1: Cortisone reductase activity inhibitory effect

Human keratinocytes (normal human epidermal keratinocyte, NHEK) were cultured in a 6-well plate incubator. After 24 hours, phosphote-buffered saline (PBS) was replaced with UVB (25 mJ / cm ² ) to irradiate, and hydrocortisone-free NHEK culture medium cortisone (10 µg / ml) and the compound represented by the following Chemical Formula 1-1 (Glucocerebrosides) (Soy, 98%), Avanti POLAR LIPIDS, Inc.) was added and cultured for 4 days. Thereafter, the cell culture solution was collected, and the cortisol concentration was measured using an ELISA method, and the results are shown in FIG. 1. Referring to FIG. 1, it can be seen that cortisol concentration is significantly increased in a cortisone-added well after ultraviolet irradiation (UVB 25 mJ / cm ² ) compared to before ultraviolet irradiation, but the compound represented by the following Chemical Formula 1-1 in the well When it is included (10 μg / ml), it can be confirmed that the concentration of cortisol does not increase significantly. From this, it can be confirmed that the composition according to one embodiment comprising the compound represented by the following Chemical Formula 1-1 as an active ingredient inhibits the activity of cortisone reductase 11β-hydroxysteroid dehydrogenase type 1.

[Formula 1-1]

Test Example 2: Cortisone reductase activity inhibitory effect

In addition, RNA was isolated from the human keratinocytes using TRIZOL, and cDNA was synthesized through RT-PCR (reverse transcriptional polymerase chain reaction). Taqman real-time PCR was performed using the synthesized cDNA to measure the gene expression levels of keratinocyte differentiation markers KRT1 and KRT10, and the results are shown in FIGS. 2 and 3 below. 2 and 3, in the case of a well containing a compound represented by Chemical Formula 1-1 (10 µg / ml), keratinocyte differentiation marker inhibited by ultraviolet (UVB) in keratinocytes (KRT10, It can be confirmed that the gene expression of KRT1) is increased. That is, it can be seen that the gene expression of keratinocyte differentiation markers inhibited by ultraviolet (UVB) in keratinocytes is restored by the compound represented by Formula 1-1, from which the formula 1-1 is expressed. It can be inferred that the gene expression of the keratinocyte differentiation marker has been restored because the compound inhibits cortisone reductase activity to reduce the cortisol concentration.

Although preferred embodiments of the present invention have been described in detail above, the scope of rights of the present invention is not limited thereto, and various modifications and improvements of those skilled in the art using the basic concept of the present invention defined in the following claims are also provided. It belongs to the scope of the invention.

Claims (6)

1. A composition for inhibiting cortisone reductase, comprising the compound represented by Formula 1 as an active ingredient:

   [Formula 1]

   

   In Chemical Formula 1,

   R ¹ to R ⁸ are each independently a hydrogen atom or a hydroxy group, and at least one of R ¹ to R ⁸ is necessarily a hydroxy group.
2. In claim 1,

   R ¹ and R ³ are each independently a hydrogen atom,

   R ² and R ⁴ to R ⁸ are each independently a hydroxy group.
3. In claim 1,

   The compound represented by Formula 1 is a soybean extract composition.
4. In claim 1,

   The cortisone reductase is a composition of 11β-hydroxysteroid dehydrogenase type 1.
5. In claim 1,

   The compound represented by Formula 1 is a composition included in a concentration range of 0.01 ㎍ / ml to 1,000 ㎍ / ml.
6. In claim 1,

   The composition is a cosmetic composition.

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